Human herpesvirus diversity is altered in HLA class I binding peptides

Area of Science:

• Immunology
• Virology
• Population Genomics

Background:

• Herpesviruses establish lifelong human infections with potential for severe pathology.
• Human leukocyte antigen (HLA) class I molecules present viral peptides to immune cells, crucial for antiviral responses.
• HLA class I allotypes vary significantly, influencing peptide binding and shaping host-pathogen interactions.

Purpose of the Study:

• To investigate if herpesvirus protein sequence diversity is influenced by HLA class I presentation.
• To determine if viral regions targeted by HLA class I exhibit different diversity patterns compared to non-targeted regions.
• To explore the role of viral latency in immune evasion strategies related to HLA presentation.

Main Methods:

• Analysis of population genomic data from Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), and Varicella–Zoster virus.
• Comparison of sequence diversity in HLA-binding versus non-binding regions of viral proteins.
• Examination of viral protein diversity across lytic and latent infection stages.

Main Results:

• Latent EBV and HCMV proteins show increased peptide sequence diversity compared to lytic proteins.
• Latent viral proteins exhibit greater population structure in HLA-binding regions than non-binding regions.
• Evidence suggests EBV adapts to local HLA environments, with reduced recognition by common HLA class I allotypes.

Conclusions:

• HLA class I peptide presentation significantly impacts the diversity and evolution of herpesviruses.
• Viral immune evasion strategies, particularly during latency, involve modifications in HLA-targeted regions.
• Understanding HLA-pathogen interactions is key to comprehending viral diversity and disease pathogenesis.